The present invention relates to the use of agonists of the glucocorticosteroid and/or mineralo-corticosteroid receptors, in particular corticosteroids, for the treatment of addictive diseases, a pharmaceutical preparation for the treatment of addictions and a method for the treatment of addictions.
Alcohol and drug addiction have been considered non-curable up to now. All therapy programs, even the new approaches of an “anti-craving” pharmacotherapy, could only support the addicted patient in his will not to have a relapse after withdrawal but they cannot reverse the core of the disease—the latent loss of control over taking of drugs. This is why the risk of a relapse is still high many years after withdrawal.
Alcohol and drug addiction (often called “dependency”) is a psychological disease with a compulsively increased self-administration of the addictive drug. The addicted consumer is not able to regulate his intake of drugs, to adjust it to his currently prevalent conditions (e.g. the present social situation) and to take alternative behaviour into consideration (American Psychiatric Association, 1994). The “loss of control”, once started, disappears only extremely slowly; even more, it seems to be spontaneously irreversible in many cases (Sobell et al., 1993). This “loss of reversibility” becomes statistically clear when looking at the extremely high percentage of relapses even after long periods of abstinence. In follow-up studies after detoxification and subsequent therapy of alcohol addicts, only a quarter up to a third, at the most, of the addicted patients remained abstinent permanently (Süβ, 1995; Veltrup et al., 1995). Spontaneous recovery success and higher percentages of long-term abstinent patients are usually due to the fact that—due to the inclusion criteria of the relevant study—not only clearly addicted patients but also “problem drinkers”, i.e. patients with excessive but still controlled alcohol consumption, were included in the study (compare Stetter and Axmann-Kremar, 1996; Wieser and Kunad, 1965). For other drugs (opiates, cocaine, amphetamine derivatives), less reliable follow-up data are available. Usually, one starts out from an even worse cure prognosis for opiate addiction than for alcohol addiction (compare Roch et al., 1992).
A comparison of different therapy approaches and treatment factors (compare Küfner, 1997) is difficult due to the fact that different therapy institutions and programs differ not only in their secondary-conditions (inclusion criteria, open and closed therapy, duration of treatment, duration of aftercare, termination criteria, documentation etc.) but also in the fact that their therapy criterion is not defined in a uniform way. The margin ranges from total abstinence to a more-or-less abstinence with few, tolerated relapses to a moderate, controlled intake of substances. If the latter was possible to a larger. extent, this would be the step back from loss of control to controlled consume. This, however, is only rarely the case. Rist (1996) refers to a meta-analysis with regard to alcoholism therapies by Süβ (1995) and the “VDR” study (Küfner and Feuerlein, 1989) according to which the percentage of non-permanently abstinent but improved patients is comparatively low. According to this, a latent addict has basically only the choice between a relapse into addiction and a continuation of abstinence while fighting the relapse all the time.
Standard forms of therapy support the patient in this fight, at the most. Since the cause for a relapse often depends on the circumstances, the main aim of many psychological and behavioural therapy approaches is the psychological and social consolidation of the patient. Also important are teaching and information, which aim at the addict being able to deal with his disease in a competent way, and, partly, specific training to cope (‘coping skills’, Rist, 1996). Conditioning and aversion progammes aim at breaking set patterns (stimulus reaction relationships connected with the taking of the substance) and/or at forming new, aversive associations with drinking alcohol and taking drugs.
Medical treatment usually is given in addition to psychotherapy or a behavioural therapy, however, partly it is also given without taking any other additional measures. Generally three fields of application can be differentiated: (a) substitution treatment, (b) anti-reward therapies and (c) anti-craving therapies. Substitution treatment was introduced in an opiate addicts years ago (Finkbeiner et al., 1996; Bühringer et al., 1997). Instead of the addictive drug (mostly heroin) the pharmacodynamically similar substitution substance (mostly methadone) is taken by the addict. This concept does not represent an addiction ‘therapy’ since craving for the original drug returns after (gradual) discontinuing with the substitute, often, also, the craving is still present during substitution in a latent way. The benefit of substitution lies more in social factors (re-integration of the addict), decriminalisation of the drug scene and reduction of morbidity and mortality.
Anti-reward-treatments with pharmaceuticals used to be similar to the aversion strategy (example: disulfiram-treatment of alcoholism). This approach was controversial in Europe for a long time but has had a revival recently (OLITA and ALITA program: Ehrenreich et al., 1997). In comparison to conventional therapy programmes the OLITA/ALITA concept is different due to an intensive ambulant long-term treatment (for two years the alcoholics patients are called in for counselling and administration of acetaldeyd-dehydrogenase-inhibiting substances for induction of an intolerance towards alcohol at the same time). The authors of the study report about a therapy success comprising approximately 50% of the patients (lasting abstinence); thus the treatment program would be more successful than standard approaches in therapy. Long-term follow-up studies, however, have not yet been carried out. A rather great, multi-center study is currently in the planning phase (oral communication).
At present, hopes are put on a medium-term blockage of the central nervous opioidergic transmission by means of the opioid-antagonists naltrexone. The addict who had previously been treated with naltrexone does not feel any effect when an opiate is administered, thus there is no rewarding effect either. This reduces the risk of relapse. The problem remains the patient's compliance, i.e. his willingness to accept the medication. Thus, the usefulness of a naltrexone therapy is controversial. Within a short- or medium-term period a naltrexone therapy seems to be effective, i.e. it can reduce the number of relapses and also have a favourable influence on the severity. This is particularly true for the treatment of alcoholics (Mann and Mundle, 1996). Lasting effects beyond the end of the pharmaceutic therapy have not yet been described.
According to definition, anti-craving medication is supposed to reduce the addict's obsessive need for his addictive drug (“craving”). There is an enormous amount of such approaches which cannot be categorised as to a common principle. The above-mentioned naltrexone-therapy, for example, is also used as an anti-craving strategy despite the fact that, with view to pharmacology, it is, probably more based on a blockage of effectiveness rather than on influencing motivation. In principle, the effects and the modes of action of the putative anti-craving drug therapy seem to be heterologous. A survey by Soyka (1997) mentions glutamate modulators, glutamate antagonists, opiate antagonists, dopamine agonists, dopamine antagonists, serotonin re-uptake inhibitors, serotonin antagonists and MAO inhibitors. Apart from the above-mentioned naltrexone with which a positive effect is likely, only the glutamate modulator acamprosate has proven to be effective in clinical tests carried out in various centres across Europe. In the German part of the study (Sass et al., 1996), at the end of the study 42% of the patients of the verum group were still abstinent after 48 weeks of treatment, in the placebo group there were only 20%. In Austria, the respective results were 30% of the acamprosate-treated patients and 21% of the placebo group (Wirtworth et al.,, 1996). There are no statistically significant data on long-term effects after discontinuing with the pharmaceutical preparation available yet. Looking at all the studies together, acamprosate about doubles the prospect—at least during the period of treatment—to remain abstinent after approximately one year of treatment. This is a success not to be underestimated. However, it remains to be said that despite acamprosate treatment approximately 70% of the addicted patients, on average in Europe, did not achieve the therapy aim of permanent abstinence (with placebo treatment there were 85%). Thus, even the up to now most effective therapeutic preparation for the treatment of addiction can be used successfully only with a small number of addicts.
The great portion of therapy failures of 60 to 90% shows that the forms of psycho, behaviour and drug therapy established today can cure the addictive disease either not at all or only insufficiently. Moreover, it has to be considered that many of the patients who stay abstinent have to fight the thought of relapse daily and organise themselves in self-help groups, such as the Alcoholics Anonymous, to support each other in their confrontation with the latent addiction (compare Schwoon, 1996). The number of those addicted patients really cured, i.e. freed from their loss of control is, thus, likely to be even lower than the figures of relapse statistics.